The purpose of this research is to determine the specificity and identity of the cytotoxic lymphocytes which are associated with the graft versus host (GVH) reaction after bone marrow transplantation (BMT) between HLA identical siblings. We shall test in two ways the hypothesis that GVH disease (GVHD) results from incompatibility for one (or two) minor alloantigen(s) that are readily recognized by cytotoxic T lymphocytes (CTL). First, we shall determine whether CTL of donor origin with specificity for a foreign minor alloantigen expressed on host cells can be isolated from patients with GVHD more readily than from patients without GVHD. Second, we shall utilize CTL with specificity for a recently discovered human minor antigen to determine whether the incidence and severity of GVHD is worse with donor-host pairs who are incompatible for this minor antigen compared with those who are compatible. Because these CTL recognize this minor antigen in association with "self" HLA-B7, this phase of the study will be conducted with donor-host BMT pairs who express B7. In addition, we shall determine the differentiation antigen profile and specificity of the cytotoxic cells that we isolate from patients with GVHD. We shall compare those which kill leukemic target cells of host type with those which kill remission cells from the same patient. Specificity of killing will be established by cold target inhibition of cytoxicity mediated by donor-derived effectors against HLA-identical host-type targets. We shall utilize monoclonal antibodies to differentiation antigens of human T-cell subsets and non-T cells in conjunction with fluorescence-activated cell sorting to establish the identity of the cytotoxic cells. Acquisition of information on these points is essential to unravel the relationship of GVH reaction and the graft versus leukemia effect and to develop a rational basis for prophylaxis of GVHD with monoclonal antibodies.